Kobayashi Shunsuke, Yasu Takeo, Momo Kenji, Ohno Nobuhiro
Dept. of Pharmacy, The Institute of Medical Science Hospital, The University of Tokyo.
Gan To Kagaku Ryoho. 2020 Jul;47(7):1063-1067.
High-dose methotrexate therapy(HDMTX)is effective against lymphoid malignancies. However, delayed elimination of methotrexate(MTX)after HDMTX administration may lead to severe adverse drug reactions. We surveyed the drugs coadministered with MTX and the incidence of delayed MTX elimination in patients treated with HDMTX in a clinical setting. We analyzed the plasma MTX concentration in 110 samples after 55 cycles of HDMTX in 33 patients. Delayed MTX elimination was defined as a plasma MTX concentration ≥1.0 mmol/L at 48 h after the start of HDMTX administration or ≥0.1 mmol/L at 72 h after the start of HDMTX administration. The incidence of the combined use of drugs affecting MTX excretion and drugs that exhibited typical renal excretion was 84.8%(n=28). The incidence of delayed MTX elimination was 39.4%(n=13). MTX-induced acute kidney injury occurred in 9 patients, all of whom also exhibited delayed MTX elimination. Therefore, when prescribing HDMTX, it is important to monitor adverse events, including acute kidney injury, which may be induced by prolonged MTX blood concentrations.
大剂量甲氨蝶呤疗法（HDMTX）对淋巴系统恶性肿瘤有效。然而，HDMTX给药后甲氨蝶呤（MTX）消除延迟可能导致严重的药物不良反应。我们在临床环境中调查了与MTX联合使用的药物以及接受HDMTX治疗的患者中MTX消除延迟的发生率。我们分析了33例患者在55个HDMTX疗程后110份样本中的血浆MTX浓度。MTX消除延迟定义为HDMTX给药开始后48小时血浆MTX浓度≥1.0 mmol/L或HDMTX给药开始后72小时血浆MTX浓度≥0.1 mmol/L。影响MTX排泄的药物与表现出典型肾脏排泄的药物联合使用的发生率为84.8%（n = 28）。MTX消除延迟的发生率为39.4%（n = 13）。9例患者发生了MTX诱导的急性肾损伤，所有这些患者也都表现出MTX消除延迟。因此，在开具HDMTX处方时，监测包括急性肾损伤在内的不良事件很重要，急性肾损伤可能由MTX血药浓度延长引起。
